title: Downregulation of Beclin 1 and impairment of autophagy in a small population of colorectal cancer.
abstract: BACKGROUND
  Autophagy is a highly conserved mechanism for degradation and recycling of long-lived proteins and damaged organelle to maintain cell homeostasis. Deregulation of autophagy has been associated with tumorigenesis. Beclin 1 is an essential autophagy protein and its upregulation has been observed in most colorectal cancer tissues. However, there is a small population of colorectal cancers with downregulation of Beclin 1.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the role autophagy plays in colorectal cancers with downregulation of Beclin 1.
  
  
  METHODS
  LC3 protein, an autophagosome marker, was assessed by ICH and WB in colorectal cancers tissues. An anti-tumor effect of Beclin 1 was examined by introducing exogenous Beclin 1 in vitro. Colony formation assay, growth curves and mouse xenograft were analysed.
  
  
  RESULTS
  Our results showed that LC3 was suppressed in the colorectal cancers (9.86 %) with downregulation of Beclin 1. Moreover, overexpression of Beclin 1 inhibited colorectal cancer cell growth and enhanced the rapamycin-induced antitumor effect in vitro.
  
  
  CONCLUSIONS
  Downregulation of Beclin 1 and autophagy inhibition play an important role in a part of colorectal cancers. Activating autophagy or overexpression of Beclin 1 may be an effective treatment for some colorectal cancers. Detection of expression profile of Beclin 1 in colorectal cancers could be a strategy for new diagnostic and therapeutic methods.
authors.affiliation: Department of Pathology, School of Basic Medicine, Central South University, 172 Tong Zi Po Road, Changsha, 410013, China, zhihong6662002@yahoo.com.cn.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Chen
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Li
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yi
authors.forename: Chang
authors.initials: C
authors.lastname: Wu
authors.forename: Junpu
authors.initials: J
authors.lastname: Wang
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Liu
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Tan
authors.forename: Jifang
authors.initials: J
authors.lastname: Wen
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism* / Q000494:pharmacology; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D015415:Biomarkers / Q000378:metabolism; D063646:Carcinogenesis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D015415:Biomarkers; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins